Langerhans cells (LC) found within the skin and mucous membranes are critical regulators of immune responses to infectious agents, allergens, and transformed cells. Among the most fundamental processes involved in immune responses in the skin are the migrations of LC from the epidermis to draining lymph nodes and the changes in LC function which ultimately lead to the presentation of antigen from the skin to lymphocytes within secondary lymphoid tissue. Preliminary studies indicate that, unlike nominal antigen, certain superantigens lead to widespread migration of LC from treated skin. In this project, superantigens will be employed in order to study the effect of antigen on LC. In order to better understand the cellular and molecular events which lead to the migration of LC from superantigen exposed skin, the cellular and molecular targets of superantigens, the fate of LC, and the signals which modulate this fate will be defined. This will be accomplished with the aid of a novel in vitro system which involves the treatment and culture of sections of mouse skin prior to the assessment of LC specific markers. Together, the results of these studies should lead to critical information concerning how superantigens induce LC depletion from treated skin. Although effects of superantigens on skin differ quantitatively from those induced by nominal antigens, the processes induced by these differing types of antigens are likely to be similar if not identical. They believe, therefore, that this project will lead to a better understanding of LC physiology and their role in complex pathological processes which occur within the skin.